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1.
Ann Surg Oncol ; 31(6): 3872-3879, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38353798

RESUMO

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.


Assuntos
Linfonodos , Metástase Linfática , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/sangue , Prostatectomia/métodos , Antígeno Prostático Específico/sangue , Pessoa de Meia-Idade , Taxa de Sobrevida , Seguimentos , Prognóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/sangue , Idoso , Linfonodos/patologia , Linfonodos/cirurgia , Excisão de Linfonodo , Estudos Retrospectivos , Estadiamento de Neoplasias , Gradação de Tumores , Margens de Excisão
2.
Jpn J Clin Oncol ; 54(4): 498-503, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38251778

RESUMO

OBJECTIVE: This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy. METHODS: A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals. RESULTS: During a median follow-up of 41.7 months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9 months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450 ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n = 37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n = 54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P = 0.021 and P < 0.001, respectively). Multivariate analysis identified testosterone level of <450 ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P = 0.007), along with high-volume disease and Gleason score 9-10. Similarly, testosterone level of <450 ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P = 0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level. CONCLUSIONS: Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Androgênios , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Testosterona , Estudos Retrospectivos , Progressão da Doença , Prognóstico
3.
J Infect Chemother ; 30(7): 579-589, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38588797

RESUMO

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.


Assuntos
Antibacterianos , Levofloxacino , Testes de Sensibilidade Microbiana , Infecções Urinárias , Humanos , Infecções Urinárias/microbiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/tratamento farmacológico , Japão/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Farmacorresistência Bacteriana , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Feminino , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/isolamento & purificação , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Monitoramento Epidemiológico , População do Leste Asiático
4.
World J Urol ; 41(3): 767-776, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36739339

RESUMO

PURPOSE: The prognosis of patients with pT3 upper tract urothelial carcinoma (UTUC) varies. The current study aimed to further classify patients with pT3 UTUC into different survival outcome groups based on tumor location and site of invasion. METHODS: This retrospective study included 323 patients with pT3 UTUC who underwent nephroureterectomy at 11 hospitals in Japan. Histological and clinical data were obtained via a chart review. Univariate and multivariate Cox proportional hazards analyses showed the effect of different variables on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median age of the patients was 72 years. Patients with pT3 UTUCs were divided into two groups: those with renal parenchymal invasion only (pT3a, n = 95) and those with peripelvic or periureteral fat invasion (pT3b, n = 228). pT3b UTUC was significantly associated with hydronephrosis, low preoperative estimated glomerular filtration rate (eGFR), histological nodal metastasis, nuclear grade 3, lymphovascular invasion (LVI), carcinoma in situ, and positive surgical margin. Based on the univariate analyses, patients with pT3b UTUC had a significantly lower 5-year RFS (42.4% vs. 70.1%, p < 0.0001), 5-year CSS (54.3% vs. 80.0%, p = 0.0002), and 5-year OS (47.8% vs. 76.8%, p < 0.0001) than those with pT3a UTUC. According to the multivariate analyses, nodal metastasis, LVI, adjuvant chemotherapy, preoperative eGFR, nuclear grade (RFS only), surgical margin (RFS only), and Charlson comorbidity index (OS only), but not pT3b stage, were associated with survival. CONCLUSION: Compared with pT3a UTUC, pT3b UTUC was significantly associated with worse histological features, consequently resulting in unsatisfactory survival outcomes.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Idoso , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Prognóstico , Nefroureterectomia/métodos , Neoplasias Urológicas/patologia
5.
Int J Urol ; 30(12): 1180-1186, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37740409

RESUMO

OBJECTIVE: Enfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV-301 trial showed its superiority to non-platinum-based chemotherapy as later-line treatment after platinum-based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum-based chemotherapy (i.e., "platinum rechallenge") in that setting. METHODS: In total, 283 patients received pembrolizumab for advanced UC after platinum-based chemotherapy between 2018 and 2023. Of them, 41 and 25 patients received EV and platinum rechallenge, respectively, as later-line treatment after pembrolizumab. After excluding two patients with EV without imaging evaluation, we compared oncological outcomes, including progression-free survival (PFS) and overall survival (OS), between the EV (n = 39) and platinum rechallenge groups (n = 25) using propensity score matching (PSM). RESULTS: Analyses on crude data (n = 64) showed no significant differences between the two groups regarding patients' baseline characteristics. PFS (5 months) and OS (11 months) in the EV group were comparable to those (8 and 12 months, respectively) in the platinum rechallenge group. After PSM (n = 36), the baseline characteristics between the two groups became more balanced, and PFS (not reached) and OS (not reached) in the EV group were comparable to those (8 and 11 months, respectively) in the platinum rechallenge group. CONCLUSIONS: EV and platinum rechallenge showed equivalent oncological outcomes, even after PSM, and both treatments should therefore be effective treatment options for post-platinum, post-pembrolizumab advanced UC.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Platina/uso terapêutico , Pontuação de Propensão
6.
Cancer Sci ; 113(7): 2386-2396, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35485635

RESUMO

The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Linfonodos/patologia , Masculino , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Estudos Retrospectivos
7.
Neurourol Urodyn ; 41(4): 1025-1030, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35325489

RESUMO

OBJECTIVE: This study aimed to determine the epidemiology of genitourinary injuries in pelvic fractures and elucidate the clinical outcomes of patients with pelvic fractures with and without genitourinary injuries at a tertiary trauma center in Japan. METHODS: Patients with pelvic fractures in our tertiary trauma center between May 2009 and April 2021 were retrospectively assessed. The patients' demographics, mechanism of injury, and hospital course details were collected. The outcomes of patients with pelvic fractures with and without genitourinary injuries were compared. RESULTS: Of 402 patients with pelvic fractures, 18 (4.5%) had genitourinary injuries. Falls were the most common mechanisms of injury for all pelvic fractures The incidence of bladder, kidney, urethral, and testis injuries were 2.0%, 1.2%, 1.2%, and 0.5%, respectively. Patients with genitourinary injuries were significantly younger (median age, 26 vs. 51 years; p < 0.001), had a higher rate of intensive care unit admission (94% vs. 58%; p = 0.002), remained hospitalized longer (median duration, 82 vs. 45 days; p < 0.001), and had a longer intensive care unit stay (median duration, 6 vs. 2 days; p < 0.001) when compared to patients without genitourinary injuries. Genitourinary injuries were not associated with in-hospital mortality. CONCLUSIONS: The incidence of genitourinary injuries with pelvic fractures was 4.5%. The presence of genitourinary injuries was associated with a higher rate of intensive care unit admission, longer hospital stay, and longer intensive care unit stay, but it was not associated with in-hospital mortality.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Adulto , Fraturas Ósseas/complicações , Fraturas Ósseas/epidemiologia , Humanos , Incidência , Masculino , Ossos Pélvicos/lesões , Estudos Retrospectivos , Uretra/lesões
8.
Jpn J Clin Oncol ; 52(1): 73-80, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34542155

RESUMO

PURPOSE: Osteoporosis is a well-known adverse effect of androgen deprivation therapy for prostate cancer. This study aimed to reveal the factors associated with the diagnosis of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy. METHODS: This retrospective cross-sectional study included 106 prostate cancer patients treated with androgen deprivation therapy. Patients with bone metastasis at the initiation of androgen deprivation therapy and those with castration-resistant prostate cancer were excluded. Bone mineral density was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Osteoporosis was defined as bone mineral density equal to or below either -2.5 SD or 70% of the mean in young adults. The association between clinicopathological variables and bone mineral density or diagnosis of osteoporosis was investigated. RESULTS: Thirty-six (34%) patients were found to have osteoporosis. The incidence of osteoporosis increased in a stepwise manner depending on the duration of androgen deprivation therapy. Multivariate logistic regression analysis identified a longer duration of androgen deprivation therapy (months, odd's ratio = 1.017, P = 0.006), lower body mass index (kg/m2, odd's ratio = 0.801, P = 0.005) and higher serum alkaline phosphatase value (U/l, odd's ratio 1.007, P = 0.014) as the factors independently associated with the diagnosis of osteoporosis. Eleven out of 50 (22%), 14 out of 35 (40%) and 11 out of 20 patients (55%) were osteoporotic in the patients with serum alkaline phosphatase values <238 U/l, 238-322 U/l and >322 U/l, respectively (P = 0.022). CONCLUSIONS: Osteoporosis is common in prostate cancer patients undergoing androgen deprivation therapy; furthermore, its incidence increases depending on the duration of androgen deprivation therapy. Bone mineral density testing should be considered for all patients on androgen deprivation therapy, especially for those with a lower body mass index and higher serum alkaline phosphatase value.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Fosfatase Alcalina , Antagonistas de Androgênios/efeitos adversos , Androgênios , Densidade Óssea , Estudos Transversais , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Estudos Retrospectivos
9.
Int J Urol ; 29(12): 1462-1469, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35996761

RESUMO

OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/patologia , Pontuação de Propensão , Estudos Retrospectivos , Estudos de Coortes , Neoplasias da Bexiga Urinária/patologia
10.
J Pharmacol Sci ; 147(1): 86-94, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34294377

RESUMO

We examined the effects of neurotensin (NTS) on the excitability of type II neurons in the rat dorsolateral bed nucleus of the stria terminalis (dlBNST) using whole-cell patch-clamp electrophysiology. Bath-application of NTS depolarized type II dlBNST neurons. Analyses of the steady-state I-V relationships implied that the depolarizing effect of NTS is due to potassium conductance blocking. The depolarizing effect of NTS was abolished in the presence of a PLC inhibitor, but not affected by a protein kinase C inhibitor. In the presence of a CaMKII inhibitor, NTS showed depolarizing effects via the increase in non-selective cation conductance in addition to the decrease in potassium conductance. Unexpectedly, in the presence of a PKA inhibitor, NTS hyperpolarized type II dlBNST neurons. These results reveal that diverse signaling pathways mediate the effects of NTS on the excitability of type II dlBNST neurons. The elevation of intracellular Ca2+ levels via the inositol phosphate-mediated signaling activates both Ca2+-dependent adenylate cyclase (AC) and CaMKII. Activation of the AC-cAMP-PKA pathway exerts depolarizing effects on type II dlBNST neurons by decreasing potassium conductance and increasing non-selective cation conductance, whereas activation of the CaMKII pathway exerts hyperpolarizing effects on dlBNST neurons by decreasing non-selective cation conductance.


Assuntos
Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Neurotensina/farmacologia , Núcleos Septais/citologia , Transdução de Sinais/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Animais , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Masculino , Técnicas de Patch-Clamp/métodos , Ratos Sprague-Dawley
11.
Jpn J Clin Oncol ; 51(10): 1577-1586, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34047345

RESUMO

PURPOSE: Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy. METHODS: The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used. RESULTS: Median patients' age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 before surgery were 50.6 and 73.2% in organ-confined disease and locally advanced disease, respectively (P < 0.0001). After surgery, they were 91.6 and 89.8%, respectively (P = 0.3896). CONCLUSIONS: Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.


Assuntos
Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Idoso , Carcinoma de Células de Transição/cirurgia , Humanos , Rim/fisiologia , Rim/cirurgia , Recidiva Local de Neoplasia , Nefrectomia , Nefroureterectomia , Prognóstico , Estudos Retrospectivos , Neoplasias Ureterais/cirurgia
12.
Eur J Neurosci ; 44(11): 2914-2924, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27690274

RESUMO

Pain is a complex experience involving sensory and affective components. Although the neuronal mechanisms underlying the sensory component of pain have been extensively studied, those underlying its affective component have yet to be elucidated. Recently, we reported that corticotrophin-releasing factor (CRF)-induced depolarization in type II neurons within the dorsolateral bed nucleus of the stria terminalis (dlBNST) is critical for pain-induced aversive responses in rats. However, the intracellular signaling underlying the excitatory effects of CRF and the contribution of such signaling to the induction of pain-induced aversion remain unclear. In the present study, we addressed these issues by conducting whole-cell patch-clamp recordings in rat brain slices and by undertaking behavioral pharmacological analyses. Intracellular perfusion of protein kinase A (PKA) inhibitor Rp-cyclic adenosine monophosphorothioate (Rp-cAMPS) or KT5720 suppressed the excitatory effects of CRF in type II dlBNST neurons, and bath application of Rp-cAMPS also suppressed it. In addition, bath application of forskolin, an adenylate cyclase (AC) activator, mimicked the effects of CRF, and pretreatment with forskolin diminished the excitatory effects of CRF. Furthermore, a conditioned place aversion (CPA) test showed that co-administration of Rp-cAMPS with CRF into the dlBNST suppressed CRF-induced CPA. Intra-dlBNST injection of Rp-cAMPS also suppressed pain-induced CPA. These results suggest that CRF increases excitability of type II dlBNST neurons through activation of the AC-cAMP-PKA pathway, thereby causing pain-induced aversive responses. The present findings shed light on the neuronal mechanisms underlying the negative affective component of pain and may provide therapeutic targets for treating intractable pain accompanied by psychological factors.


Assuntos
Adenilil Ciclases/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Dor/metabolismo , Núcleos Septais/metabolismo , Transdução de Sinais , Animais , Carbazóis/farmacologia , Colforsina/farmacologia , Condicionamento Clássico , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Masculino , Dor/etiologia , Dor/fisiopatologia , Pirróis/farmacologia , Ratos , Ratos Sprague-Dawley , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/fisiologia
13.
J Pharmacol Sci ; 131(2): 141-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27179939

RESUMO

We investigated electrophysiological properties of human induced-pluripotent-stem-cell-derived and embryonic-stem-cell-derived cardiomyocytes, and analyzed action potential parameters by plotting their frequency distributions. In the both cell lines, the distribution analysis revealed that histograms of maximum upstroke velocity showed two subpopulations with similar intersection values. Sub-populations with faster maximum upstroke velocity showed significant prolongation of action potential durations by application of E-4031, whereas others did not, which may be partly due to shallower maximum diastolic potentials. We described electrophysiological and pharmacological properties of stem-cell-derived cardiomyocytes in the respective sub-populations, which provides a way to characterize diverse electrical properties of stem-cell-derived cardiomyocytes systematically.


Assuntos
Potenciais de Ação/fisiologia , Células-Tronco Embrionárias/citologia , Miócitos Cardíacos/fisiologia , Células-Tronco Pluripotentes/citologia , Linhagem Celular , Humanos , Técnicas de Patch-Clamp
14.
Glob Health Med ; 6(3): 199-203, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38947410

RESUMO

In recent years, randomized controlled trials have demonstrated that upfront androgen receptor signaling inhibitors (ARSIs) prolong overall survival (OS) compared with androgen deprivation therapy (ADT) alone or combined androgen blockade (CAB) in patients with metastatic castration-sensitive prostate cancer (mCSPC). However, it remains unclear whether upfront ARSI is superior to CAB in Asian populations, among which the efficacy of ADT/CAB is considered relatively high. In this study, we compared the oncological outcomes of upfront ARSI and CAB in Japanese patients with mCSPC. Patients with mCSPC who underwent systemic therapy between May 2009 and October 2023 were enrolled retrospectively. Propensity score matching (PSM) was performed to compare the castration-resistant prostate cancer-free survival (CRPC-FS), cancer-specific survival (CSS), and OS between patients treated with upfront ARSI (ARSI group) and those treated with CAB (CAB group). In total, 30 and 142 patients were enrolled in the ARSI and CAB groups, respectively. After PSM (25 patients in each group), CRPC-FS was significantly longer in the ARSI group than in the CAB group (median: 36.7 vs. 12.3 months, hazard ratio: 0.44, 95% confidence interval: 0.20-0.97, p = 0.035). No significant differences were observed in CSS or OS between the two groups. In conclusion, when compared to CAB, upfront ARSI might have the potential to extend CRPC-FS among individuals in the Japanese population.

15.
Clin Genitourin Cancer ; 22(3): 102094, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38714434

RESUMO

BACKGROUND: To date, no studies have compared the treatment outcomes of second-line therapies in patients with metastatic clear cell renal cell carcinoma (ccRCC). This study retrospectively evaluated the efficacy of cabozantinib and axitinib as second-line treatments in patients with metastatic ccRCC who previously received immune-oncology combination therapy. PATIENTS AND METHODS: Patients with metastatic ccRCC treated with cabozantinib and axitinib as second-line therapy after nivolumab-ipilimumab treatment were identified among 243 patients with RCC treated between August 1, 2018 and January 31, 2022 at 34 institutions belonging to the Japanese Urological Oncology Group. Patients were assessed for treatment outcomes, including progression-free survival (PFS), overall survival, objective response rate (ORR), and incidence rate of treatment-related adverse events (AEs). RESULTS: Forty-eight patients treated with cabozantinib and 60 treated with axitinib as second-line therapy after nivolumab-ipilimumab treatment for metastatic ccRCC were identified. The median PFS (95% confidence interval) was 11.0 months (9.0-16.0) with cabozantinib and 9.5 months (6.0-13.0) with axitinib. The ORRs were 37.5% (cabozantinib) and 38.3% (axitinib). The rates of any-grade AEs and grade ≥3 AEs were 79.2% (cabozantinib) versus 63.3% (axitinib; P = .091) and 35.4% (cabozantinib) versus 23.3% (axitinib; P = .202), respectively. In the poor-risk group, PFS was longer in the cabozantinib group than in the axitinib group (P = .033). CONCLUSION: The efficacy and safety of cabozantinib and axitinib were comparable. In the poor-risk group, cabozantinib was more effective than axitinib. These findings provide valuable insights into the selection of second-line treatment options after nivolumab-ipilimumab treatment in patients with metastatic ccRCC.


Assuntos
Anilidas , Protocolos de Quimioterapia Combinada Antineoplásica , Axitinibe , Carcinoma de Células Renais , Ipilimumab , Neoplasias Renais , Nivolumabe , Piridinas , Humanos , Axitinibe/uso terapêutico , Axitinibe/administração & dosagem , Axitinibe/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Masculino , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Feminino , Estudos Retrospectivos , Anilidas/administração & dosagem , Anilidas/uso terapêutico , Anilidas/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Ipilimumab/administração & dosagem , Ipilimumab/uso terapêutico , Ipilimumab/efeitos adversos , Idoso , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Resultado do Tratamento
16.
J Nanobiotechnology ; 11: 11, 2013 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-23575365

RESUMO

The interface between engineering and molecular life sciences has been fertile ground for advancing our understanding of complex biological systems. Engineered microstructures offer a diverse toolbox for cellular and molecular biologists to direct the placement of cells and small organisms, and to recreate biological functions in vitro: cells can be positioned and connected in a designed fashion, and connectivity and community effects of cells studied. Because of the highly polar morphology and finely compartmentalized functions of neurons, microfabricated cell culture systems and related on-chip technologies have become an important enabling platform for studying development, function and degeneration of the nervous system at the molecular and cellular level. Here we review some of the compartmentalization techniques developed so far to highlight how high-precision control of neuronal connectivity allows new approaches for studying axonal and synaptic biology.


Assuntos
Microtecnologia/métodos , Nanotecnologia/métodos , Neurobiologia , Animais , Axônios/metabolismo , Caenorhabditis elegans , Drosophila melanogaster , Microfluídica/métodos , Modelos Animais , Neurônios/citologia , Neurônios/fisiologia
17.
IJU Case Rep ; 6(6): 398-401, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37928304

RESUMO

Introduction: Retroperitoneal tumors account for 0.2% of all neoplasms. Among these tumors, retroperitoneal vascular malformations are particularly rare, with most previously reported cases being venous malformations. Case presentation: A 72-year-old woman was diagnosed with a retroperitoneal tumor on abdominal computed tomography. The 27-mm diameter tumor was located away from the right kidney and major vessels in the right perirenal adipose tissue. Contrast-enhanced computed tomography revealed a heterogeneously enhanced tumor with well-defined borders. Dynamic contrast-enhanced magnetic resonance imaging revealed rapid enhancement in the arterial phase and a progressive filling-in pattern in the delayed phase. Although vascular malformation was suspected, a definitive diagnosis could not be established. The retroperitoneal tumor was excised laparoscopically for therapeutic and diagnostic purposes, and the histopathological diagnosis confirmed it as a capillary arteriovenous malformation. Conclusion: Herein, we presented a rare case of retroperitoneal capillary arteriovenous malformation that was difficult to definitively diagnose preoperatively.

18.
IJU Case Rep ; 6(1): 30-32, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36605699

RESUMO

Introduction: Primary prostate lymphomas are very rare; however, the incidence of malignant lymphoma is high among HIV-infected patients. Herein, we report a case of primary diffuse large B-cell lymphoma (DLBCL) of the prostate in an HIV-infected patient. Case presentation: A 47-year-old man presented with miction pain and back pain. Abdominal CT revealed a huge prostate mass extending to the left retroperitoneum. Serum sIL-2R level was abnormally high (2896 U/mL), whereas PSA level was normal. HIV antigen and antibody tests were positive. The patient was diagnosed with DLBCL after a prostate biopsy. Systemic treatments were administered; however, the tumor was refractory, and the patient died 9 months after diagnosis. Conclusion: Prostate malignant lymphomas are rare but should be considered in patients with enlarged prostates and normal PSA levels. It should be noted that HIV patients have a high incidence of malignant lymphomas.

19.
J Geriatr Oncol ; 14(6): 101558, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37327760

RESUMO

INTRODUCTION: The Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are established screening tools for assessing vulnerability in older patients. Here we investigated their usefulness as predictors of length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery. MATERIALS AND METHODS: This study included 643 patients who underwent urological surgery (74% were for malignancy) at our institute from 2017 to 2020. G8 and VES-13 scores were routinely recorded upon admission. These indices and other clinical data were obtained through chart review. The correlation between G8 group (high, >14; intermediate, 11-14; low, <11) or VES-13 group (normal, <3; high, ≥3) and length of total hospital stay (LOS), postoperative hospital stay (pLOS), and postoperative complications including delirium were analyzed. RESULTS: The median patient age was 69 years. A total of 44%, 45%, and 11% of patients were classified into high, intermediate, and low G8 groups, respectively, while 77% and 23% were classified into normal and high VES-13 groups, respectively. Univariate analyses revealed that low G8 scores were associated with prolonged LOS (vs. intermediate, odds ratio [OR] 2.87, P < 0.001; vs. high, OR 3.87, P < 0.001), prolonged pLOS (vs. intermediate, OR 2.37, P = 0.005; vs. high, OR 3.06, P < 0.001), and delirium (vs. intermediate, OR 3.23, P = 0.007; vs. high, OR 5.38, P < 0.001), and high VES-13 scores were associated with prolonged LOS (OR 2.85, P < 0.001), prolonged pLOS (OR 2.97, P < 0.001), and Clavien-Dindo grade ≥ 2 complications (OR 1.74, P = 0.044), and delirium (OR 3.18, P = 0.001). Furthermore, multivariate analyses revealed that low G8 and high VES-13 scores were independent factors which predicted prolonged LOS (low G8; vs. intermediate, OR 2.96, P < 0.001; vs. high, OR 3.94, P < 0.001; high VES-13; OR 2.98, P < 0.001) and prolonged pLOS (low G8; vs. intermediate, OR 2.41, P = 0.008; vs. high, OR 3.18, P = 0.002; high VES-13; OR 3.47, P < 0.001), respectively. DISCUSSION: The G8 and VES-13 may be effective tools for predicting prolonged LOS/pLOS and postoperative complications in Japanese patients who undergo urological surgery.


Assuntos
Delírio , Avaliação Geriátrica , Neoplasias , Idoso , Humanos , Delírio/epidemiologia , Delírio/etiologia , População do Leste Asiático , Tempo de Internação , Neoplasias/patologia , Complicações Pós-Operatórias/epidemiologia
20.
In Vivo ; 37(6): 2849-2853, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905637

RESUMO

BACKGROUND/AIM: We present a case of solitary fibrous tumor, arising from the diaphragm in the retroperitoneal space, that was resected with robotic assistance. CASE REPORT: An 85-year-old female patient was referred to our hospital for evaluation of a suspected right renal tumor. Abdominal contrast-enhanced computed tomography revealed a tumor (maximum diameter, 36 mm) protruding from the superior pole of the right kidney. The patient was scheduled for robot-assisted, retroperitoneoscopic, partial nephrectomy based on a preoperative diagnosis of renal cell carcinoma. Intraoperative findings revealed that the tumor originated from the diaphragm and had no continuity with the renal parenchyma. Pathological examination revealed a solitary fibrous tumor. CONCLUSION: Solitary fibrous tumors are rare soft-tissue neoplasms with a distinct molecular feature of the fusion of nerve growth factor-inducible A gene-binding protein 2 with signal transducer and activator of transcription 6 gene (NAB2::STAT6). We believe that this is the first reported case of a solitary fibrous tumor arising from the diaphragm in the retroperitoneal space.


Assuntos
Hemangiopericitoma , Tumores Fibrosos Solitários , Feminino , Humanos , Idoso de 80 Anos ou mais , Diafragma/diagnóstico por imagem , Diafragma/cirurgia , Espaço Retroperitoneal/patologia , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/cirurgia , Tórax , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Biomarcadores Tumorais
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